Chatzimichail, S., Casey, D., & Salehi-Reyhani, A. (2019). Zero electricalpower pump for portable high-performance liquid chromatography. Analyst,144(21), 6207-6213. https://doi.org/10.1039/c9an01302d

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ISSN 0003-2654

PAPER Stelios Chatzimichail, Duncan Casey and Ali Salehi-Reyhani Zero electrical power pump for portable high-performance liquid chromatography

Analystrsc.li/analyst

Volume 144 Number 21 7 November 2019 Pages 6145–6448

Analyst

PAPER

Cite this: Analyst, 2019, 144, 6207

Received 11th July 2019,Accepted 24th August 2019

DOI: 10.1039/c9an01302d

rsc.li/analyst

Zero electrical power pump for portable high-performance liquid chromatography

Stelios Chatzimichail,a Duncan Casey b,c and Ali Salehi-Reyhani *a,c

A major trend in analytical chemistry is the miniaturization of laboratory instrumentation. We report a

pump requiring no power to operate based on the controlled expansion of a pre-pressurised gas for use

in portable applications of high-performance liquid chromatography. The performance of the gas pump

is characterised and integrated into a compact liquid chromatography system capable of isocratic separ-

ations integrating an LED-based UV-absorption detector. The system weighed 6.7 kg when the mobile

phase reservoir was fully charged with 150 mL solvent and included an on-board computer to control the

system and analyse data. We characterise the flow-rate through chromatography columns with a variety

of geometries and packing materials for a range of pressures up to 150 bar. The maximum variation in

flow rate was measured to be 6.5 nL min−1, limited by the resolution of the flow detector. All tests were

made on battery power and results are a mixture of those made in the laboratory and in the field.

Additionally, we performed a series of 1 m drop tests on the device and show the system’s high tolerance

to mechanical shocks during operation in the field.

Introduction

High performance liquid chromatography (HPLC) is a goldstandard analytical technique crucial to many industriesworldwide in its ability to separate and identify chemicals in acomplex mixture. LC systems that are portable are becomingincreasingly attractive in their ability to perform measure-ments at the point of sampling. This has potential in field-based applications relating to water and food security;however, conventional LC systems are not suited to point-of-sampling analyses primarily due to their size and lack ofrobustness outside controlled laboratory conditions.Furthermore, there are significant pressures to minimising thecost of implementing field-based solutions in resource-poorsettings. There are four core components of any LC system – 1,an eluent pump to drive the sample and mobile phase; 2, aninjector assembly to introduce the crude sample onto the sep-aration phase; 3, a column which separates analytes within thesample; and 4, a detector to record and ideally quantify thesample’s individual components as they leave the column. Inthis work, we focus on the development of a pump system thatenables miniaturization of the overall platform.

The pursuit of field-based chemical analysis has a longhistory and is exemplified by early attempts to develop portablechromatography systems. The OB-4 chromatograph reported byBaram et al. in 1983 had dimensions of 70 cm × 30 cm × 50 cm(width × depth × height) and weighed 42 kg.1 In a follow-upreport in 1996, they used an iteration of their field chromato-graph that weighed 14 kg.2 Similar efforts were reported byTulchinsky and St Angelo in 1998 with the a battery-operatedportable which weighed 9.5 kg, not including the requisitesolvent reservoirs or computer for acquisitions.3 In a similarvein, conventional HPLC systems have been installed in mobilevehicle-based laboratories in order to move the point of testingcloser to the site of sampling. Each of these approaches hasmajor limitations and has typically added to rather than reducedthe complexity of the system in order to provide electrical powerand improve the instruments’ robustness to shocks in the field.

Demonstrations of miniaturized LC of varying capability havebeen made over the last few years and represent a step-change insize and capability of portable solutions. Ishida et al. presented acompact electroosmotic pumping system used in conjunctionwith a microfluidic chip based column and electrochemicaldetector.4 The system was not able to achieve high pressure andfell short of LC pressures (0.75 MPa) restricting the choice ofchromatographic columns and resulting in long analysis times,even for exemplar separations. Importantly it was the first demon-stration of a completely integrated system incorporating a micro-fluidic chip being lightweight with an overall weight of 2 kg, notincluding the requisite computer system. Gu et al. have reportedan electroosmotic pump capable of generating pressures exceed-

aDepartment of Chemistry, King’s College London, Britannia House, 7 Trinity Street,

London, SE1 1DB, UK. E-mail: ali.salehi-reyhani@kcl.ac.ukbBristol Centre for Functional Nanomaterials, HH Wills Physics Laboratory, Tyndall

Avenue, Bristol, BS8 1TL, UKcDepartment of Chemistry, Imperial College London, SW7 2AZ, UK.

E-mail: ali.salehi-reyhani@imperial.ac.uk

This journal is © The Royal Society of Chemistry 2019 Analyst, 2019, 144, 6207–6213 | 6207

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ing 1200 bar (120 MPa) that show incredible potential in support-ing miniaturised LC.5,6 However, electroosmotic pumps requirehigh-voltages which necessitate bulky external power supplies,currently defeating the portability afforded by a microfluidic LC.Sharma et al. have characterized isocratic and gradient-basedsystems incorporating a compact nano-flow pump in a setup withpotential for portability that could generate pressures in excessof 50 MPa. They demonstrated the reverse-phase isocratic separ-ation of a series of alkyl benzenes and gradient separation of athree-component mixture of pesticides.7,8 The detector wasinitially lamp based which limited the potential for miniaturiza-tion; however, in a follow up report, an UV-LED based absorp-tion detector was built and helped achieve sub-parts-per-milliondetection limits for adenosine-5′-monophosphate (AMP), amonomer in the production of RNA.9 UV-LEDs have been anenabling technology for miniaturised LC, with emissions as fardown as 235 nm having been reported alongside methods toadequately stabilise their emission.10 Commercial systemsbased on the works cited here have been developed.

In general, however, groups seeking to miniaturize LCsystems have done so by shrinking the size of conventionalcomponents. This introduces increased cost and complexity inmanufacturing and has potential impacts upon reliability andconsistency. The growing need for field-based or point-of-caremeasurements is best supported by miniaturized systems thatnot only maintain or exceed the typical performance of theirlab-based counterparts but to do so in an affordable and there-fore accessible manner. In this paper we report important stepstoward achieving portable, high-performance and affordable LCthrough an approach to miniaturization of the high-pressurepump. Examples of low-pressure pneumatic pumping (up toapprox. 6 bar) have been previously reported in open tubularion chromatography systems; however, field-portable instru-ments have yet to be reported.11 The pumping mechanismexploits the latent potential energy of a pressurized gas and sohas no electrical power requirements, making it highly amen-able in supporting field-portable LC. We demonstrate thatsolvent may be driven through commercial narrow-bore LCcolumns by exploiting the controlled expansion of a pre-pressur-ized gas. Incorporating a gas “pump”, we have engineered anisocratic UV-absorption HPLC system the size of a small brief-case (Fig. 1). It is a stand-alone system, requiring only modestbattery (6.5 Ah) power to support all on-board flow rate andpressure sensors, an absorption detector and computing unitwith all necessary solvents being stored on-board. In this report,we characterize the pressure-flow behaviour of the device, itsseparation capability and demonstrate its resistance to mechan-ical shocks. All results are presented from data acquired on thedevice free from mains power, predominantly in the field.

ExperimentalReagents

Analytical or HPLC grade solvents and chemicals were used aspart of this work. Ultra-pure water was generated on-site (18.2

MΩ; Milli-Q system, Millipore). Isopropanol, L-tryptophan(≥98%) and L-tyrosine (≥98%) were purchased from Sigma-Aldrich. The mobile phase was 50 : 50 (v/v) acetonitrile andwater with 0.01% formic acid. Stock solutions of the aminoacids were stored in the dark at 4 °C for a maximum of 7 days.

Instrumentation

The miniaturised LC system incorporates componentry toachieve high-performance liquid chromatography – (1) a pumpand injector assembly, (2) a separation column, and (3) a flowcell and detector (Fig. 1). The system has a form factor of330 mm (width) × 290 mm (depth) × 140 mm (height) andweighs 6.7 kg when fully charged with solvent, including allrequisite computer systems and battery modules. The systemand its connections are schematically depicted in Fig. 1A.Pump. The pressurised gas source was a nitrogen (oxygen-free)cylinder (BOC, UK) with a maximum fill pressure of 230 bar.This was used to fill a high pressure (3000 psi) 426 mL air tank(Tippmann; BZ Paintball Supplies, UK). The tank was con-nected via flexible tubing to a ball-valve assembly whichallowed head pressure to be vented to atmosphere or trans-mitted through to the 150 mL mobile phase reservoir(Swagelok, UK). The connections to and upstream of themobile phase reservoir were a combination of pipe fittings(Swagelok, UK) and stainless-steel tubing (Swagelok, UK).Downstream of the reservoir PEEK tubing and zero deadvolume fittings were used to connect components. In thesystem reported here, the solvent reservoir is in direct contactwith the gas pressurising the system head. This may preclude

Fig. 1 Portable high-performance liquid chromatography. (A) Theschematic shows the key system components and their connectivity.The components are depicted for clarity and are not intended to dictatean orientation of operation. (B) Photograph of the ‘chromatography in asuitcase’ system running separations in the field.

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the use of certain combinations of gas and mobile phaseowing to outgassing as the pressure drops through the system.This is problematic for the post-column detector where thepassage of evolving gas bubbles alters the level of light absorp-tion. Techniques such as enhanced-fluidity LC involves theaddition of liquefied CO2 to conventional liquid mobilephases and has been shown to provide enhanced diffusivity,faster solute mass transfer, and reduced systembackpressure.12,13 We have not, as yet, explored how this effectmight be exploited using our system. We have found the lowsolubility of nitrogen permits the driving of mobile phasewithout necessitating a physical barrier or membrane toisolate the phases. To monitor the pressure in the system headup to a pressure of 400 bar a pressure transducer was fitted(Swagelok, UK) and connected to a tablet form-factor PC(Microsoft, UK) via an analog-to-digital converter (USB 6210,National Instruments; USA). Battery operation typically allowsfor operation times of 13 hours. The most significant limitingfactor in the battery lifetime was the tablet computer employedto run laboratory development software. This could beextended significantly with the adoption of low-power single-board microprocessor systems. Injector. A 6-port injector witha 2 µL internal sample injection loop (Rheodyne 7725; IDEXCorporation, USA) was used to inject samples into the flowline. A guard column was fitted immediately downstream ofthe injector. Chromatography. Isocratic separations of theamino acids were performed using a range of reverse-phaseC18 packed capillary, packed standard and monolith columns(length × inner diameter, packing): 30 mm × 150 µm, 3 µm(Agela, China); 70 mm × 150 µm, 5 µm (Agela, China); 80 mm× 150 µm, 5 µm (Agela, China); 150 mm × 1.0 mm, 5 µm(Sigma, UK); and 150 mm × 100 µm, monolith (Chromolith;Merck, UK). Detector. Analytes were detected based on theirUV-absorption. The light source was a commercially available275 nm UV-LED (UVTOP275; Ocean Optics, UK) fibre-coupledto a z-type flow cell with a 2 µL internal volume and 10 mmpath length (Ocean Optics, UK). A miniaturised spectrometer(USB2000; Ocean Optics, UK) was fibre-coupled to the outputof the flow-cell and used as the detector, which allowed forspectral discrimination without the need for additional filters.Electronics & Data acquisition. Data was acquired usingcustom-written code in LabView. Absorption was calculated bylog10(I0/I) where I and I0 are the intensity of light transmittedthrough the sample and the initial light intensity measured atthe baseline, respectively. For each run, system head pressureand mobile phase flow rate was recorded with each chromato-gram. The spectrometer recorded at 10 Hz and the data weresample-averaged every 1 s.

Results and discussionPump performance

One of the working principles in HPLC is the predictability ofsolvent flow rate through the system in order to achieve charac-teristic analyte retention times. If the profile of how flow rate

changes as a function of time is known, it is possible in a sim-plified isocratic system to computationally compensate for thisby post-processing chromatograms. Of course, achievingprecise flow rates from the outset is desirable. In our system,solvent is driven through microfluidic tubing by the controlledexpansion of a pressurised gas. In order to test the gas pump’sperformance, we attached the system to a lab-based industrialgas cylinder (Nitrogen (Oxygen free), 9.3 m3 tank volume, BOCUK) which allowed us to pressurise the head of the system in afacile manner without the need to detach and fill gas car-tridges for each desired pressure; it also allowed us to measurethe response of the flow rate to controlled jumps in pressure.

In determining the capability of the pump, the flow rate ofsolvent through a range of packed capillary columns inaddition to a monolith column was measured (Fig. 2A).Despite their advantages for portable systems capillarycolumns have not been adopted to any significant degree.Here we exploit their features of small size, high efficiency andlow solvent consumption by incorporating them into the porta-ble LC system. The system head was pressurised to a desiredpressure between 0 and 150 bar and isolated from the cylinderusing a valve. The 6-port injector valve was subsequently set toconnect the pump via the sample loop to the downstream flui-dics, and the mobile phase under pressure in the fluid reser-voir flowed through the column. The gas pressure in thesystem head and fluid flow rates through the columns weremonitored for a minimum duration of 100 s (typically 300 s)before testing subsequent pressures. A linear increase in flowrate as a function of increasing cylinder pressure was observedspanning ∼50 nL min−1 to ∼1 μL min−1, dependent on thecolumn’s geometry and packing type. In the present device,the pressure is directly controlled and, as expected, an increasein pressure leads to a higher flow rate for all the columnstested (Fig. 2A). Predictably, the lowest flow rates weremeasured for the columns with the highest back pressures.The operational range of flow rates is limited by the backpressure of the system, predominantly dictated by the dimen-sions of the column. By employing wider bore (>2 mm IDcolumns), flow rates approaching the mL min−1 range may beachieved. A caveat being the significantly higher consumptionof solvent, which can be an issue for portable LC.

We then tested the response of solvent flow rate in thesystem to both positive and negative jumps in pressure(Fig. 2B). To achieve an increase in pressure, the cylinder valvewas opened and the cylinder regulator pressure increased untilthe desired pressure was indicated by the digital pressuretransducer, not the regulator. To decrease pressure, a ventvalve was opened briefly, and the flow rate was equally asresponsive to drops in pressure. Pressure jumps were achievedby operating manual valves and regulator and were completedin under 5 s. The response in change of flow rate to changes inpressure was immediate (<1 s; Fig. 2C) and expected byPascal’s principle of transmission of fluid-pressure. It is antici-pated that the use of digital or electronically operated valveswould reduce the time to complete jumps in pressure, ifnecessary.

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A drawback in employing syringe pumps to drive a mobilephase is their pulsatile behaviour at low flow rates and thetime required for flow to stabilise. Due to the reciprocalswitching behaviour of the driving pistons in a typical com-mercial HPLC pump, pulsatile flow can develop in the flowrate of the mobile phase. This leads to synchronous baselinefluctuations which can limit the sensitivity of the system.Pulse dampeners are almost universally employed to smooththe pressure-flow profile yet are unable to fully flatten them.We calculated the variation in mobile phase flow rate aboutthe mean for a range of gas pressures up to 150 bar (Fig. 2D).To determine the baseline variation of the pressure transducerand flow sensor, the variation of flow rate about the mean wascalculated when the system head was not pressurised i.e. at 0bar. The peak to peak variation in flow rate was invariant overthe pressure range tested. Since we do not measure variations inflow rate above the instrument noise floor even at the highestmeasured flow rates, we expect the flow rate fluctuation to bewell below the absolute peak to peak variation of 6.5 nL min−1.We therefore concluded that we did not observe pulsatile flowin the gas-pumped system and the measured variation inpressure and mobile phase flow rate was limited by the resolu-tion of the pressure transducer and flow rate sensor. For themaximum measured flow rates, the flow precision was ≤0.2%RSD. This compares favourably to current market solutions forresearch-grade reciprocating pumps, particularly given the lowcost and amenability of a gas pump to portable LC.

Chromatographic separations

Although, amino acid analysis is considered to be the goldstandard for quantitative peptide and protein analysis, alterna-tive methods are often chosen due to their relatively lowercost, complexity and assay time. Such analyses tend to be per-formed using colorimetric methods in routine biochemistry ornitrogen determination in food analysis.14,15 For the latter, theChinese milk scandal of 2008 revealed the vulnerability ofstandard methods to verify the protein content in milk-basedinfant formulas based on their inability to discriminateprotein from other nitrogen-rich chemicals, oradulterants.16–18 Comprehensive amino acid analysis is necess-ary in a wide range of biologically facing research but it can bechallenging to achieve sufficient sensitivity and selectivitywithout chemical derivatisation steps.19–21 Reports of derivati-sation-free methods have been made22,23 and so the portablesystem reported here has potential in widening access to LC-based protein quantification methodologies.

The system’s ability to perform chromatographic separ-ations was tested. The reverse-phase separation of a two-com-ponent mixture of the aromatic amino acids tryptophan andtyrosine was performed (Fig. 3A) owing to their favourableabsorption at 275 nm, the peak wavelength of the UV-LED whichserves as the light source in the UV-absorption detector. Theseresults were measured in a stand-alone fashion whereby the LCsystem was operated on battery power (6.5 Ah) and the gaspump is supported by a gas cartridge (426 mL fill volume). Thegas cartridge was pre-pressurised with nitrogen gas to 100 bar.

Fig. 2 Pump performance. (A) The mobile phase flow rate is measuredthrough a set of capillary columns over a range of system pressures, upto 150 bar. Figure legend specifies the column length, inner diameterand packing type; each column was packed with reverse-phase silica.The error bars lie within the points. (B) An exemplar time-resolved traceof mobile phase flow rate for a series of pressure jumps. (C) Twozoomed in time-resolved trace of a pressure jump where the blackarrowheads labelled (i) and (ii) in (B) denote the start of each trace. Thechange in flow rate tracks the change in system pressure. (D) The vari-ation in flow rate is plotted for a range of system pressures. Themaximum peak to peak variation is 6.5 nL min−1 and invariant over thepressure range tested.

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The retention times of the analytes were 95.3 ± 0.4 s fortyrosine (n = 3) and 172.9 ± 1.1 s for tryptophan (n = 3). Usingthe half-peak height method, the column (100 mm) generated1407 and 1819 theoretical plates for tyrosine and tryptophan,

respectively; the peak symmetry factor was found to be 1.87and 1.31 for tyrosine and tryptophan, respectively. To deter-mine the limit of detection (LOD) of the system the baselinevariation was measured (n = 4) to be 3.96 × 10−4 AU by flowingmobile phase only (Fig. 3B). The signal to noise ratio (SNR)can be defined as S/σN, where S is the peak intensity and σN isthe standard deviation of the baseline signal; the SNR of50 µM tyrosine and tryptophan was 1340 and 4100, respect-ively. A concentration series was established by injectingknown concentrations of tryptophan ranging from 2.4 µM to49.0 µM (Fig. 3C). Defined as 3.3σN/s, where s is the slope ofthe calibration curve, the LOD of tryptophan of 24.1 nM, or<25 ppb.

Pyrimethanil and thiabendazole are fungicidal pesticideswhich are applied post-harvest to fruits in order to limit spoi-lage and increase their shelf-life. Exposure to pesticides is ahealth concern, therefore, maximum residue levels are set inorder to ensure safe and appropriate agricultural practice.Where in use, too little pesticide may lead to resistance infungal strains thereby limiting their efficacy. Administration ofthe correct dosage, then, is essential and by extension so areaccurate and reliable methods to monitor their levels. Thereare approximately 300 million central laboratory HPLC testsperformed globally per year for the food safety sector. In thecase of perishable foodstuffs where there may be a limitedtime window for testing, field tests are one approach to widen-ing the scope of these tests in monitoring the amount of pesti-cides entering the supply chain. A separation of a mix of1.4 mM pyrimethanil and 1.06 mM thiabendazole was per-formed (Fig. 3D). It is evident that the pesticides are beingdetected and separated, although with the conditions usedhere to a resolution short of the baseline. The retention timesof the analytes were 381.3 ± 4.2 s for thiabendazole (n = 3) and482.3 ± 5.6 s for pyrimethanil (n = 3).

Longevity of pump

During the course of a chromatographic run the pre-pres-surised gas expands into the mobile phase reservoir in orderto drive fluid through the system. As it does so the pressure inthe gas reservoir and system head will reduce. A drop inpressure will in turn lead to a commensurate drop in mobile-phase flow rate from run to run. Whether the degree to whichthis occurs is significant will be in part dictated by the ratio ofthe volume of the gas cartridge (Vcartridge) and system head(Vhead) to the volume of mobile phase required for each run(Vrun); this is determined by the volume of the downstreamfluidics, the mobile phase flow rate and the separation timerequired. In the embodiment in Fig. 1, the volume of the flui-dics downstream of the solvent reservoir is 39.3 μL (300 μm IDtubing) in addition to the full volume of the column; thisranged from 0.4 μL (ID 100 μm, length 50 mm) to 78.5 μL (ID1 mm, length 100 mm). The volume of the gas cartridge of426 mL and the system head is 24.8 mL. For the separations inFig. 3A, it is estimated that a 300 s separation time will requireapproximately 350 ± 5 µL for the steel column employed ofdimensions ID 1 mm and length 100 mm (flow rate 70 ± 1 µL

Fig. 3 Separations are performed on the system using the pressurised-gas pump. (A) A mix of the amino acids tryptophan and tyrosine are sep-arated and identified using a UV-LED absorption detector arrangement.The mix trace is vertically shifted for clarity. (B) The baseline noise of thedetector is shown. (C) A concentration series is established plotting peakheights for tryptophan spanning 2.4 µM (4.8 pmol) to 49.0 µM (98pmol). The error bars lie within the points. (D) A mix of the pesticides (i)thiabendazole and (ii) pyrimethanil are separated.

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min−1). In this case the ratio of Vrun : (Vcartridge + Vhead) is 7.76 ×10−4. Therefore, such a small ratio ensures a minimal drop inpressure per chromatographic run.

This ratio is helpful to understand the number of runs forwhich the pumping strategy presented here could supportbefore cumulative drops in pressure preclude the analyticalgoals of a chromatographic separation. How such constraintsmanifest will be application specific; however, for our pur-poses here it is helpful ascertain a ballpark estimate of whenthis might occur. For example, this might be governed by theabsolute change in retention time for specific peaks orperhaps a time limit necessary to complete a chromatographicrun. One might arbitrarily impose a constraint that the gaspressure must not drop below 90% of the initial fill-pressure.In this case, one may predict approximately 128 (1 mm IDcolumn) to 13 870 (100 μm ID column) supported chromato-graphic runs for the system described above dependent on thecolumn employed. These estimates are promising for field-based applications. As is typical for lab-based HPLC, employ-ing 4.6 mm ID columns, for instance, flow rates on the orderof 1.0 mL min−1 may be achieved due to lower back pressures;however, the solvent required per run results in much fewersupported chromatographic runs, approximately only 10–20.

In terms of longevity, this suggests that the gas pump asreported is better suited to driving solvent through capillarycolumn-based systems. The number of runs over which thepump may be considered useful in the example of the capillarycolumn greatly exceeds the number of runs over which atypical column itself is generally considered to withstand.

To control flow, the system head may be isolated from thedownstream fluidics by closing a ball valve. Flow through thesystem can be fully halted by operating a valve downstream tothe column but, to prevent inadvertent damage to optical com-ponents, is placed upstream of the flow cell.

Mechanical stability

Due to the environment in which it will inevitably operate, arequirement of a portable LC platform is to be more mechani-

cally stable than its lab-based counterpart. In our portable LCsystem incorporating a gas pump, curiously, the only movingcomponents are the injector assembly and the mobile phaseitself flowing through the fluidics. It is reasonable to expectthat this may confer a good measure of mechanical stability tothe device overall and result in a relatively low susceptibility tovibrations or physical impacts. We tested this by performing aseries of 1 m vertical drop tests during operation (Fig. 4). Thebaseline noise after the impact was insignificantly different tothat prior to impact suggesting that the drops had minimal orno effect on its operation. No published results of mechanicalstability or impact analysis on HPLC systems are available andso no comparative assessment of our system is possible.Instrument manufacturers are known to conduct packagingtesting to simulate mechanical shocks when being shipped,during which the instruments are not under operation.

Conclusions

A major obstacle to miniaturisation of LC is the pump due tothe onerous and simultaneous requirements for it to be small-form factor, achieve high-pressure and support stable flow –

and achieve this in very challenging environments outside of alab. We have shown how the controlled expansion of a pre-pressurised gas may be utilised to perform the role of a pumpin a high-performance liquid chromatography system. Thiswork characterises the pressure-flow characteristics of amobile phase driven by the gas pump and demonstrates itsuse in a miniaturised, lightweight, portable LC system per-forming reverse-phase separations in the field. In addition tosatisfying the requirements above, exploiting the latent energyof a pre-pressurized gas has the major advantage of not requir-ing power to operate; thereby significantly reducing therequirements of the battery. This in turn can lead to a muchsmaller class of fully integrated devices. Given the cost of a gaspump is considerably cheaper than conventional pumps, weexpect this work to be of interest to those seeking to supportor develop field-based applications that are also cost-sensitive.

The isocratic separation and detection of analytes isexpected to be useful in a number of applications demon-strated here without compromising system performance.Although this work has demonstrated the feasibility of theplatform, several key engineering challenges remain. Forinstance, developing the system to be capable of gradient-based separations would help to broaden the range of appli-cations, particularly to ones involving more complex mixtures.Of course, the operating environment is a very important con-sideration in portable LC applications and there should ideallybe componentry to either control the internal environment ofthe instrument or active compensation mechanisms to varypressure and/or flow rate. Given the low power requirements ofour system it is possible to accommodate on-column orsolvent reservoir heating elements to improve the system’s resi-lience to environmental factors. We predict that the microflui-

Fig. 4 Mechanical stability of the device is tested by repeated 1 m droptests. Traces (n = 3) show the baseline absorbance before and afterimpact. The grey vertical bar indicates the approximate time at whichthe device is released and impacts the floor. No change in baselineabsorbance mean or variance is observed as a result of the drop tests.

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dic volumes of the separation system would help in ensuring agood thermal response to such control mechanisms.

Conflicts of interest

ASR has a financial interest in intellectual property and com-mercialisation efforts related to the platform described here.

Acknowledgements

This work was supported by the Engineering and PhysicalScience Research Council (EPSRC) through a fellowship (EP/S001603/2) and Impact Assessment Award (EP/R511559/1) toASR.

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